Case ReportMonomorphic Ventricular Tachycardia as a Presentation of GiantCell Myocarditis

Michael H. Chiu , Cvetan Trpkov, Saman Rezazedeh, and Derek S. Chew

Libin Cardiovascular Institute of Alberta, Cummings School of Medicine, University of Calgary, Alberta, Canada

Correspondence should be addressed to Michael H. Chiu; michael.chiu@ahs.ca

Received 4 January 2019; Revised 5 April 2019; Accepted 27 May 2019; Published 19 June 2019

Academic Editor: Man-Hong Jim

Copyright © 2019 Michael H. Chiu et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Background. Idiopathic giant cell myocarditis (GCM) has a fulminant course and typically presents in middle-aged adults withacute heart failure or ventricular arrhythmia. It is a rare disorder which involves T lymphocyte-mediated myocardialinflammation. Diagnosis is challenging and requires a high index of suspicion since therapy may improve an otherwiseuniformly fatal prognosis. Case Summary. A previously healthy 54-year-old female presented with hemodynamically significantventricular arrhythmia (VA) and was found to have severe left ventricular dysfunction. Cardiac MRI demonstrated acutemyocarditis, and endomyocardial biopsy showed giant cell myocarditis. She was treated with combined immunosuppressivetherapy as well as guideline-directed medical therapy. A secondary prevention implantable cardioverter defibrillator (ICD) wasimplanted. Discussion. GCM is a rare, lethal myocarditis subtype but is potentially treatable. Combined immunosuppressionmay achieve partial clinical remission in two-thirds of patients. VA is common, and patients should undergo ICD implantation.More research is needed to better understand this complex disease. Learning Objectives. Giant cell myocarditis is anincompletely understood, rare cause of myocarditis. Patients present predominately with heart failure and dysrhythmia.Diagnosis is confirmed by histopathology, and immunosuppression may improve outcomes. ICD implantation should beconsidered. In the absence of treatment, prognosis is poor with a median survival of three months.

1. Introduction

Idiopathic giant cell myocarditis is a rare clinical entity firstrecognized in the early 1950s [1]. GCM has a fulminantcourse with an autoimmune pathophysiology in virus-negative GCM [2, 3]. Often fatal due to arrhythmia or heartfailure, two-thirds of patients exhibit response to immuno-suppressive therapy, and some undergo cardiac transplanta-tion [2]. We report a case of a previously healthy femalediagnosed with idiopathic giant cell myocarditis.

2. Case Report

A previously healthy 54-year-old female presented to emer-gency services with acute onset of malaise, nausea, palpita-tions, and presyncope. Her ECG showed monomorphicventricular tachycardia at 230 bpm, and she underwent suc-

cessful cardioversion. Hemodynamic stability was restored,and she was admitted to the cardiac intensive care unit.

Initial cardiovascular examination was pertinent for apositive abdominojugular reflux sign and a third heart sound.There was no clinical evidence of pulmonary or systemiccongestion or low cardiac output state, and no other manifes-tations of systemic disorders were present.

ECG in sinus rhythm revealed a nonspecific intraventric-ular conduction delay with a QRS duration of 130ms, a Pwave of 1mm in the lead II, a PR interval of 166ms, and aQTc of 507ms at a heart rate of 96 bpm. Transthoracic echo-cardiography showed left ventricular systolic dysfunctionwith an estimated ejection fraction of 35%, preserved rightventricular function, and no valvular abnormalities (aorticroot dimension of 2.9 cm, left atrium of 3.2 cm, LV diastoleof 4.9 cm, LV systole of 4.0 cm, fractional shortening of18.6%, interventricular septum of 0.85 cm, posterior wall of0.78 cm, left atrium volume index of 36.3ml/m2, left

HindawiCase Reports in CardiologyVolume 2019, Article ID 7276516, 4 pageshttps://doi.org/10.1155/2019/7276516

ventricular mass of 79.3 grams/m2, left ventricular outflowtract diameter of 2.2 cm, stroke volume of 39.9ml, end dia-stolic volume (MOD-bp) of 128.5ml, ejection fraction(MOD-bp) of 31.1%, cardiac output (LVOT) of 4.9 l/min,stroke volume (LVOT) of 57.3 cc, TAPSE of 2.2 cm, and RVS’ velocity of 11.5 cm/sec). Coronary arteries were angio-graphically normal. On cardiac magnetic resonance imaging,there was extensive, midwall patchy late gadoliniumenhancement consistent with acute myocarditis (Figure 1).

A serum blood work revealed a hemoglobin count of141 g/l with an MCV of 92fl, a platelet count of 182 × 109/l,a WBC of 12 3 × 109/l with a differential (neutrophil 8 2 ×

109/l, lymphocytes 2 8 × 109/l, monocytes 0 9 × 109/l, eosino-phils 0 3 × 109/l, and basophils 0 1 × 109/l), a high-sensitivitytroponin T of 46 ng/l, an NT-proBNP of 261ng/l, an ESR of11mm/h, and a CRP of 3.2mg/l. An infectious panel wasnegative for cytomegalovirus, Epstein–Barr virus, hepatitisB, hepatitis C, herpes simplex virus, HIV, mumps, toxoplas-mosis, and varicella.

Right ventricular endomyocardial biopsy was performed.This demonstrated features typical of GCM, including exten-sive myocyte damage, multinucleated giant cells, and mixedinflammatory cell infiltrate. There was no granuloma forma-tion (Figure 2). Autoimmune and connective tissue disease

(a) (b)

(c) (d)

(e) (f)

Figure 1: Cardiac myocardial resonance imaging demonstrating late gadolinium enhancement of the basal to midanterior, anteroseptal,inferoseptal, and inferior segments and apical inferior segments of the left ventricle. Patchy enhancement within the septum on the side ofthe ventricle: (a) 2-chamber view (b) 3-chamber view (c) 4-chamber view, (d) short-axis view at the base, (e) short-axis view at the level ofthe papillary muscles, and (f) short-axis view at the level of the apex.

2 Case Reports in Cardiology

serology was unremarkable (negative anti-nuclear antibody,glomerular basement membrane antibody, anti-neutrophilcytoplasmic antibody, myeloperoxidase antibody, proteinase3 antibody, and lymphotoxic antibody screening). Anti-heartautoantibodies were not tested on the patient and may be alimitation in the diagnosis of GCM.

The patient was treated with standard heart failure ther-apy including a beta-blocker, angiotensin receptor inhibitor,and mineral corticoid receptor antagonist. Once the diagno-sis of GCM was confirmed, a combined immunosuppressivetherapy with high-dose prednisone (60mg daily), tacrolimus(alternating doses of 1mg and 2mg daily), and mycopheno-late mofetil (1000mg BID) was added. She also underwentimplantation of a secondary prevention dual chamber ICD.In total, the diagnosis of GCM was established within 8 daysof presentation, immunosuppressive therapy prescribed onday 9, and ICD implanted on day 14. Total hospital staywas 16 days, and there was no recurrence of VA or heart fail-ure progression. She was discharged in stable condition andremained NYHA II at her follow-up appointments. Her

echocardiogram at 6 and 12 months is unchanged withsevere LV systolic dysfunction with minor regional variabil-ity and mild RV dysfunction. Repeat biopsy performed at 6months demonstrated interstitial fibrosis and myocytehypertrophy. Currently, our patient remains on her currentimmunosuppressive therapies aside from a tapering of hersteroid dose to 5mg daily.

3. Discussion

Idiopathic giant cell myocarditis (GCM) is presumed to be aT lymphocyte-mediated inflammatory disorder. An associa-tion with other autoimmune disorders such as thyroiditisand myasthenia gravis has been reported; however, it wasfound only among 20% of patients in a larger contemporarycase series [2]. GCM affects men and women equally, with amean age of onset of 42.6 years reported in the multicenterGCM study registry [2]. Common presentation includesheart failure and VA; however, it can also present as an acutemyocardial infarction mimic or atrioventricular block [4].

(a) (b)

(c) (d)

(e) (f)

Figure 2: Pathological slides from the endomyocardial biopsy: (a) damaged and normalmyocardium, (b) normalmyocardium, (c) multinucleatedgiant cells (H&E staining 20x), (d) multinucleated giant cells (H&E staining 40x), (e) mixed inflammatory cells, and (f) eosinophils.

3Case Reports in Cardiology

Many cases are clinically diagnosed as idiopathic cardio-myopathy until autopsy or cardiac transplantation confirmsGCM by histopathology [4]. Differential diagnosis includessarcoidosis, but granulomata formation, which is absent inGCM, differentiates the two diseases. Repeated endomyocar-dial biopsy may be necessary to diagnose GCM, with highersensitivity early in the disease process and in more fulminantcases with more extensive myocardial involvement [4, 5].EMB has a reported sensitivity of 80% with a positive predic-tive value of 71% that increases with repeat biopsy [5]. Rightventricular septum was noted to be the target in most casesfor myocardial sampling [4]. Imaging modalities such asechocardiography reveal reduced LV function and dilation.Contrast-enhanced cardiac MRI typically reveals areas of lategadolinium enhancement (scar) and increased T2-weightedsignal (myocardial edema). 18FDG-PET shows the areas ofperfusion defects and inflammation and may be utilized totarget biopsies to the sites of active inflammation [4].

Prognosis is poor with a median survival of 3 months inthe absence of treatment. Sole corticosteroid use was associ-ated with an improved survival of 3.8 months. Combinedimmunosuppression may be more effective than corticoste-roids alone with a median survival of 11.5 months with ste-roids plus azathioprine and 12.6 months with cyclosporine[2, 4]. GCM is known to recur in transplanted hearts withinfiltrates identified on biopsy at a mean of 3 years posttrans-plant [2, 6]. There are limited data to guide long-term treat-ment strategies; however, it may be necessary to continueimmunosuppression indefinitely due a relapse risk describedeven eight years after initial diagnosis [7]. Idiopathic GCM isan organ-specific autoimmune disease thought to be due toautoimmunity to myosin, thus necessitating an individual-ized immunosuppressive regimen with most cases requiringlifelong therapy.

Although seemingly effective, combined immunosup-pression achieves partial clinical remission in only two-thirds of patients and EMB frequently shows ongoing inflam-mation. The lack of complete remission suggests the patho-physiology, and optimal treatment is not fully understood[3, 4, 8]. GCM recurrences have even been reported amongpatients who underwent heart transplantation [4, 9]. Despitemedical therapy, sustained VA is present in up to 50% ofpatients and ICD implantation is recommended [2, 4].

Experimental models have suggested that there may betwo forms of giant cell myocarditis with macrophage-derived giant cells and with myocyte-derived giant cellswith the appearance of multinucleated giant cells corre-sponding to the fulminant phase of inflammation andmyocardial damage [10]. Diagnosis is typically made viaendomyocardial biopsy. Combined immunosuppressive ther-apy, implantable cardioverter defibrillators, and guideline-based heart failure therapies improve the overall prognosis;however, more research is needed to better understand thiscomplex disease.

Consent

The patient has agreed and provided consent for this casereport.

Conflicts of Interest

The authors do not report any conflicts of interest.

Authors’ Contributions

All authors participated in the care of this patient and con-tributed in the preparation of the figures and manuscript.

References

[1] B. Kean and M. T. Hoekenga, “Giant cell myocarditis,” TheAmerican Journal of Pathology, vol. 28, no. 6, pp. 1095–1105,1952.

[2] L. T. Cooper, G. J. Berry, and R. Shabetai, “Idiopathic giant-cellmyocarditis — natural history and treatment,” New EnglandJournal of Medicine, vol. 336, no. 26, pp. 1860–1866, 1997.

[3] L. T. Cooper Jr., J. M. Hare, H. D. Tazelaar et al., “Usefulness ofimmunosuppression for giant cell myocarditis,” The AmericanJournal of Cardiology, vol. 102, no. 11, pp. 1535–1539, 2008.

[4] R. Kandolin, J. Lehtonen, K. Salmenkivi, A. Räisänen-Soko-lowski, J. Lommi, and M. Kupari, “Diagnosis, Treatment, andOutcome of Giant-Cell Myocarditis in the Era of CombinedImmunosuppression,” Circulation: Heart Failure, vol. 6,no. 1, pp. 15–22, 2013.

[5] R. C. Shields, H. D. Tazelaar, G. J. Berry, and L. T. Cooper Jr.,“The role of right ventricular endomyocardial biopsy for idio-pathic giant cell myocarditis,” Journal of Cardiac Failure,vol. 8, no. 2, pp. 74–78, 2002.

[6] V. V. Menghini, V. Savcenko, L. J. Olson et al., “Combinedimmunosuppression for the treatment of idiopathic giant cellmyocarditis,” Mayo Clinic Proceedings, vol. 74, no. 12,pp. 1221–1226, 1999.

[7] J. J. Maleszewski, V. M. Orellana, D. O. Hodge, U. Kuhl, H.-P. Schultheiss, and L. T. Cooper, “Long-term risk of recur-rence, morbidity and mortality in giant cell myocarditis,” TheAmerican Journal of Cardiology, vol. 115, no. 12, pp. 1733–1738, 2015.

[8] L. T. Cooper and C. ElAmm, “Giant cell myocarditis,” Herz,vol. 37, no. 6, pp. 632–636, 2012.

[9] W. Gries, D. Farkas, G. Winters, and M. Costanzo-Nordin,“Giant cell myocarditis: first report of disease recurrence inthe transplanted heart,” The Journal of Heart and Lung Trans-plantation, vol. 11, no. 2, pp. 370–374, 1992.

[10] M. Kodama, Y. Matsumoto, M. Fujiwara et al., “Characteristicsof giant cells and factors related to the formation of giant cellsin myocarditis,” Circulation Research, vol. 69, no. 4, pp. 1042–1050, 1991.

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